PROJECT 1: Assessing and modulating the role of inflammation and fibrosis in the dystrophic process. Project 1 will follow the fate of satellite cells during the progression of disease in mdx and A/J mice, while characterizing changes in muscular tissue, fibrosis and fat. The project will go on to analyze inhibitors of inflammation and/or fibrosis and their impact on disease pathology in mdx and A/J mice. Lastly, the project will examine the combined effects of combined anti-inflammatory or anti-fibrotic drugs and myostatin inhibitors. The fundamental concept driving this project is that limiting fibrosis in the muscular dystrophies will help extend the period of successful regeneration via the patients own satellite cell repair, increase the benefits associated with therapies that increase the patients' muscle repair capacity, and will extend the age at which patients can benefit from eventual viral gene or stem cell therapies. Thus the primary objectives of this project are the attainment of clinically useful pharmacological means of inhibiting fibrosis by identifying the best existing pharmacological inhibitors of fibrosis, as well as driving the development of new classes of inhibitors.